The country has mixed public and private healthcare systems. The Ministry of Health (MOH) is currently the major provider and financier of health services. There are more than 484 hospitals across the country. According to Saudi health laws, all Saudi citizens and visitors should be fairly provided with comprehensive and accessible health services. The MOH is responsible for establishing guidelines and strategies for the diagnosis and management of diseases.

Regarding DMD care, the standardization of diagnosis and treatment is considered inadequate and understated. The current diagnostic pathways vary because of the availability of genetic testing and specialized doctors. Patients who live in big cities are most likely to get diagnosed, genetically confirmed with DMD, and treated for complications. In contrast, people who live in small cities or rural areas could be missed and need to be referred to the nearest specialized hospitals for proper diagnosis and treatment. Gratefully, funding for diagnostic tests and treatment is available and supported by the government for Saudis, and by health insurance coverage for non-Saudis.

In Saudi Arabia, autosomal recessive disorders are the most common type of genetic disorders (17). Previous reports have shown that approximately 2–5% of all reported monogenic disorders in the KSA are X-linked disorders (18, 19). Moreover, a recent study published by the Centre for Arab Genomic Studies (CAGS) showed that musculoskeletal disorders represent less than 5% of the genetic disorders in the KSA, corresponding to the expected trend of genetic disorders in the Arab population (14).

Globally, DMD affects 1 in 5,000 newborn males (20, 21). The prevalence of the disease is slightly less than 10 cases per 100,000 males (20, 22). On the other hand, the incidence of BMD is 1 in 20,000 male births (10). The incidence and prevalence of DMD have never been reported. It is relatively difficult to determine the incidence and prevalence of DMD/BMD based on the available information; namely, the information is outdated, and there is no updated registry of patients with DMD/BMD. Additionally, at the time of this writing, large-scale epidemiological studies have yet to be published. Therefore, national demographic information is not currently available. Finally, it is highly recommended that a national registry of DMD/BMD patients be established as a keystone for future epidemiological studies as well as treatment and preventive programs.

The dystrophin gene (DMD; OMIM #300377) is located on the short arm of the X chromosome near the region Xq21 and consists of 79 identified exons, which makes it one of the largest human genes (23, 24). DMD patients exhibit changes in the DMD gene, preventing the expression of the muscle isoform of dystrophin (Dp427m) (10, 25, 26). On the other hand, in-frame deletions within the DMD gene cause Becker muscular dystrophy (BMD; OMIM #300376), a milder form of DMD (10, 25).

Deletions, duplications, and point mutations (nonsense mutations) are the most predominant mutations detected in patients with DMD (27, 28). Deletions represent 60–70% of DMD pathogenic variants, while duplications and point mutations represent 5–10 and 20%, respectively (26, 28, 29). Exons 45–55 and exons 3–9 are known as “hotspot” regions where approximately two-thirds of deletions and duplications leading to DMD/BMD are clustered (26, 28, 29).

The variants patterns within DMD have been investigated in different ethnic groups (30–35). Over the last three decades, limited studies on the pathogenic variants of DMD/BMD in Saudi Arabia have been published (Table 1). In 2002, a study showed that deletion of one or more exons was detected in 63% (26 out of 41) of patients with DMD and BMD in the central region of Saudi Arabia (36). A later study conducted in the Western region showed that 62.5% (5 out of 8) of patients with DMD and BMD carried exon deletions within exons 45–55 (37). A subsequent study conducted in the same part of the country reported that deletions were detected in 40% (6 out of 15) of males with DMD, where 20% of the deleted exons contained exon 51 (38). A recent study showed that deletions and duplications represented 46.3 and 53.7%, respectively, of the pathogenic variants in investigated males with DMD (39).

Although the outcomes of these studies are valuable and consistent with those of DMD/BMD investigations in other populations, robust characterization of DMD alterations in the Saudi population still needs to be performed. First, the number of participants reported in the published studies as a percentage of the country’s population is substantially low. Second, most of the available data are limited to patients from the central and western regions, while similar investigations have not been performed in the remaining eleven regions. Third, genetic variations in Saudi female carriers have never been reported. Fourth, genetic variations in exons other than exons 45–55 and exons 3–9 have yet to be screened. This is important because ethnicity and genetic background determine genetic defects in many diseases. In conclusion, regional and national studies incorporating advanced techniques, such as whole-exome sequencing (WES) and Sanger sequencing, are critically needed to elucidate the patterns of DMD among patients and carriers in Saudi Arabia.

Guidelines for diagnosing DMD are available and should be followed (12, 40) (Figure 1). According to published articles about care considerations sponsored by the United States Centers for Disease Control and Prevention (CDC), a diagnosis of DMD should be made as early as possible once signs and symptoms become noticeable, usually at approximately 2–5 years of age (12, 40). The diagnosis process starts with determining the creatinine kinase (CK) level as well as concentrations of other serum enzymes, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (40). Genetic testing is the first confirmatory test for the diagnosis (42). Finally, muscle biopsies for dystrophin staining are recommended for further confirmation for those with clinically compatible dystrophinopathy but with negative genetic findings (11, 12, 43).

The time until intervention and accurate diagnosis significantly impacts effective treatment and prognosis for DMD patients (11, 12, 43). In Saudi Arabia and Middle Eastern countries, a lack of awareness, specific resources, expertise, and standardized diagnostic pathways results in missing the opportunity for early interventions to control the disease (44). Compared with European countries such as the UK, the average delay in DMD diagnosis in Middle Eastern countries is 2–3 years (44). In the UK, the mean age at diagnosis is 4.3 years, while in Middle Eastern countries, the average age at DMD diagnosis is 7–8 years (44). The diagnosis of DMD is also considered late in Middle Eastern countries when compared with Asian countries such as China (5.0 years), Korea (5.0 years), and Taiwan (5.6 years) (45–47).

In Saudi Arabia, a study of the clinical characteristics of Saudi DMD patients revealed a delay in diagnosis due to a lack of awareness of early symptoms (39). The same study showed that 69.8% of participants showed early signs of DMD at 1–3 years of age; however, approximately 44% were diagnosed at 9–12 years of age. Furthermore, a study of four reported cases concluded that the lack of a standardized referral pathway, awareness and specific logistics results in misdiagnosis and delayed diagnosis of DMD in males (16). An observational study of individuals with DMD showed that the mean age at genetic diagnosis of DMD in Saudi Arabia is 6.9 years (42). Unfortunately, there are no standardized referral pathways for DMD patients in the country (44).

In conclusion, the current literature shows that DMD is diagnosed later in Saudi Arabia than in other countries. The country lacks expert clinicians in rare genetic diseases such as DMD. In addition, specialized medical centers for diagnosis and treatment have yet to be established. Patients who live in remote areas of the kingdom face difficulties in accessing specialized health centers, leading to a delayed diagnosis or misdiagnosis of uncommon diseases.

Screening programs for identifying children with DMD/BMD have been suggested. The initial screening test evaluates the serum level of CK. For instance, in the United States, newborn screening for DMD has become mandatory in New York and Ohio, with the goal of expansion to include other states.

Currently, two screening programs exist and are carried out by the Ministry of Health (MOH): premarital and newborn screening programs (48). The newborn screening program was established in 2005 and was expanded in 2016 to include other newborn diseases. However, neuromuscular diseases have not yet been included in the program.

Considering the delay in diagnosis, rate of consanguinity, and lack of awareness, carrier testing could also be a good strategy for early intervention and prevention. Screening for asymptomatic and symptomatic female carriers who have a family history of DMD is seemingly not considered. The identified carriers could be provided with consultation services such as pre-implementation and prenatal genetic testing, improving the health status of the next generation.

Generally, standardized treatment strategies for DMD patients are relatively insufficient. Currently, there is no cure for the disease, and the primary goal of treatments is delaying disease progression. In Saudi Arabia, glucocorticoids such as prednisone and deflazacort are regularly prescribed to slow muscle degeneration and improve muscle function (11, 44). In addition, management measures for DMD in Saudi Arabia include treating cardiovascular and respiratory complications, gastrointestinal and nutritional complications, and rehabilitation (15, 36).

Although glucocorticoids may not be appropriate for long-term use, newer molecular and genetic therapies have the potential to restore the normal function of dystrophin. The variant-specific therapies ataluren and eteplirsen have already been approved by the European Commission for use within the European Union and the US Food and Drug Authority, respectively (49). Other emerging treatments targeting dystrophin function and normal expression are close to obtaining regulatory approval or have recently been approved (Table 2). Whether these treatments will be available to patients in Saudi Arabia and how those patients will be evaluated and qualify for the therapies are still unknown.

The management of DMD patients should not be limited to treatment plans and clinical interventions. Management should extend throughout their lives and include their families since the disease is also linked to cognitive abnormalities and social challenges. In general, patients with such diseases are eligible for education and financial and social support in Saudi Arabia. Specialized social workers and social programs are recommended to support patients with untreatable diseases such as DMD.

Despite the challenges in this field, there are potential opportunities for sustainable improvements. The establishment of national and regional research programs is strongly recommended to form a basis for strategic decisions. For instance, funding national screening studies of the prevalence and incidence of DMD in the Saudi population is needed for establishing healthcare facilities and research centers. Moreover, conducting large-scale studies to characterize the genetic variability and common DMD alterations in Saudi DMD patients is essential. This knowledge would assist in building a database of standardized treatment strategies and support future clinical trials searching for newer therapeutic approaches.

National efforts to raise awareness of the disease are also essential. Parents and families should be aware of the early signs and symptoms of DMD and how to treat and support affected children and adults. Finally, DMD is still untreatable, and more international collaborative efforts are recommended to offer better support to patients with this disease worldwide.

Tips for ongoing improvements, programs for:

Updating standard of care

Updating awareness of DMD among medical multispecialty community

Updating awareness of DMD care among patients and families